Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model

Detalhes bibliográficos
Autor(a) principal: Trigo, Gabriela
Data de Publicação: 2013
Outros Autores: Martins, Teresa G., Fraga, Alexandra G., Longatto Filho, Adhemar, Castro, António G., Azeredo, Joana, Pedrosa, Jorge
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/25080
Resumo: Author Summary: Buruli Ulcer (BU), caused by Mycobacterium ulcerans, is a necrotizing disease of the skin, subcutaneous tissue and bone. Standard treatment of BU patients consists of a combination of the antibiotics rifampicin and streptomycin for 8 weeks. However, in advanced stages of the disease, surgical resection of the destroyed skin is still required. The use of bacterial viruses (bacteriophages) for the control of bacterial infections has been considered as an alternative or a supplement to antibiotic chemotherapy. By using a mouse model of M. ulcerans footpad infection, we show that mice treated with a single subcutaneous injection of the mycobacteriophage D29 present decreased footpad pathology associated with a reduction of the bacterial burden. In addition, D29 treatment induced increased levels of IFN-γ and TNF in M. ulcerans -infected footpads, correlating with a predominance of a mononuclear infiltrate. These findings suggest the potential use of phage therapy in BU, as a novel therapeutic approach against this disease, particularly in advanced stages where bacteria are found primarily in an extracellular location in the subcutaneous tissue, and thus immediately accessible by lytic phages.
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spelling Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad modelScience & TechnologyAuthor Summary: Buruli Ulcer (BU), caused by Mycobacterium ulcerans, is a necrotizing disease of the skin, subcutaneous tissue and bone. Standard treatment of BU patients consists of a combination of the antibiotics rifampicin and streptomycin for 8 weeks. However, in advanced stages of the disease, surgical resection of the destroyed skin is still required. The use of bacterial viruses (bacteriophages) for the control of bacterial infections has been considered as an alternative or a supplement to antibiotic chemotherapy. By using a mouse model of M. ulcerans footpad infection, we show that mice treated with a single subcutaneous injection of the mycobacteriophage D29 present decreased footpad pathology associated with a reduction of the bacterial burden. In addition, D29 treatment induced increased levels of IFN-γ and TNF in M. ulcerans -infected footpads, correlating with a predominance of a mononuclear infiltrate. These findings suggest the potential use of phage therapy in BU, as a novel therapeutic approach against this disease, particularly in advanced stages where bacteria are found primarily in an extracellular location in the subcutaneous tissue, and thus immediately accessible by lytic phages.This work was supported by a grant from the Health Services of Fundacao Calouste Gulbenkian, and the Portuguese Science and Technology Foundation (FCT) fellowships SFRH/BPD/64032/2009, SFRH/BD/41598/2007, and SFRH/BPD/68547/2010 to GT, TGM, and AGF, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Public Library of ScienceUniversidade do MinhoTrigo, GabrielaMartins, Teresa G.Fraga, Alexandra G.Longatto Filho, AdhemarCastro, António G.Azeredo, JoanaPedrosa, Jorge20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/25080eng1935-27271935-273510.1371/journal.pntd.0002183info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:09:01ZPortal AgregadorONG
dc.title.none.fl_str_mv Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model
title Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model
spellingShingle Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model
Trigo, Gabriela
Science & Technology
title_short Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model
title_full Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model
title_fullStr Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model
title_full_unstemmed Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model
title_sort Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model
author Trigo, Gabriela
author_facet Trigo, Gabriela
Martins, Teresa G.
Fraga, Alexandra G.
Longatto Filho, Adhemar
Castro, António G.
Azeredo, Joana
Pedrosa, Jorge
author_role author
author2 Martins, Teresa G.
Fraga, Alexandra G.
Longatto Filho, Adhemar
Castro, António G.
Azeredo, Joana
Pedrosa, Jorge
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Trigo, Gabriela
Martins, Teresa G.
Fraga, Alexandra G.
Longatto Filho, Adhemar
Castro, António G.
Azeredo, Joana
Pedrosa, Jorge
dc.subject.por.fl_str_mv Science & Technology
topic Science & Technology
description Author Summary: Buruli Ulcer (BU), caused by Mycobacterium ulcerans, is a necrotizing disease of the skin, subcutaneous tissue and bone. Standard treatment of BU patients consists of a combination of the antibiotics rifampicin and streptomycin for 8 weeks. However, in advanced stages of the disease, surgical resection of the destroyed skin is still required. The use of bacterial viruses (bacteriophages) for the control of bacterial infections has been considered as an alternative or a supplement to antibiotic chemotherapy. By using a mouse model of M. ulcerans footpad infection, we show that mice treated with a single subcutaneous injection of the mycobacteriophage D29 present decreased footpad pathology associated with a reduction of the bacterial burden. In addition, D29 treatment induced increased levels of IFN-γ and TNF in M. ulcerans -infected footpads, correlating with a predominance of a mononuclear infiltrate. These findings suggest the potential use of phage therapy in BU, as a novel therapeutic approach against this disease, particularly in advanced stages where bacteria are found primarily in an extracellular location in the subcutaneous tissue, and thus immediately accessible by lytic phages.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/25080
url http://hdl.handle.net/1822/25080
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1935-2727
1935-2735
10.1371/journal.pntd.0002183
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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